Redox potentials and drug discovery

A paper just out, that set me thinking a bit about are we missing a trick or two, discusses redox potentials of hydroxycinnamic acids such as caffeic and ferulic acid this are of particular current interest in health because of their anti-oxidant activity. It’s estimated that this class may constitute one third of the phenolic compounds in our diet. The paper determines redox potentials for a range of these acids alongside their antioxidant activity showing that they correlate with each other and allows development of structure property activity relationships.

All this is well and good assuming stuffing ourselves with anti-oxidants really is a good thing, though I will keep drinking the red wine just in case, but what about use of redox potentials more generally in drug design – are we missing a trick. My past experience and from what I see in the literature I generally read is very little use of the technique to help understand how our molecules will behave – when I tried to get some redox potentials measured while working in big pharma I was told the kit was no longer available – note the no longer. I guess where I am coming from is can we use measured redox potentials as part of our understanding of improving stability of molecules in aggressive redox environments particularly within metabolic enzymes. A quick look on google did pick up this thesis sponsored by Roche looking at developing high throughput redox measurement techniques. The starting point they come from is that redox potentials can be considered equivalents of ionisation potentials. So could we be looking at some sort of cascade of calculated ionisation potentials during in silico design followed by redox potentials after synthesis and who knows perhaps exploit electrochemistry during synthesis another under used area perhaps? It would be good to hear people’s thoughts on this.